Plexins and semaphorins are a large family of proteins that are involved in cell movement and response. The importance of plexins and semaphorins has been emphasized by their discovery in many organ systems including the nervous (Nkyimbeng-Takwi and Chapoval, 2011; McCormick and Leipzig, 2012; Yaron and Sprinzak, 2012), epithelial (Miao et al., 1999; Fujii et al., 2002), and immune systems (Takamatsu and Kumanogoh, 2012) as well as diverse cell processes including angiogenesis (Serini et al., 2009; Sakurai et al., 2012), embryogenesis (Perala et al., 2012), and cancer (Potiron et al., 2009; Micucci et al., 2010). Plexins and semaphorins are transmembrane proteins that share a conserved extracellular semaphorin domain (Hota and Buck, 2012). The plexins and semaphorins are divided into four and eight subfamilies respectively based on their structural homology. Semaphorins are relatively small proteins containing the extracellular semaphorin domain and short intracellular tails. Plexins contain the semaphorin domain and long intracellular tails (Hota and Buck, 2012). The majority of plexin and semaphorin research has focused on the nervous system, particularly the developing nervous system, where these proteins are found to mediate many common neuronal cell processes including cell movement, cytoskeletal rearrangement, and signal transduction (Choi et al., 2008; Takamatsu et al., 2010). Their roles in the immune system are the focus of this review.
Animals ; Cell Adhesion Molecules ; immunology ; metabolism ; Humans ; Immunity ; Nerve Tissue Proteins ; immunology ; metabolism ; Semaphorins ; immunology ; metabolism

Neisseria gonorrhoeae (NG), as a pathogen of gonorrhea, is strictly limited to growth on the human host. In case of gonococcal infection, the body may recruit such inflammatory cells as neutrophils to resist the invasion of NG or initiate its adaptive immune response by antigen presentation to eliminate the pathogen. However, a series of immune escape mechanisms of NG make it difficult to clear up the infection. In the innate immune system, NG can not only secrete thermonuclease to degrade neutrophile granulocytes, inhibit respiratory burst to resist killing by neutrophils, activate NLRP3 to prompt the pyronecrosis of inflammatory cells, but also regulate the differentiation of macrophages to reduce the inflammatory response, combine with factor H to evade complement-mediated killing. NG infection can hardly give rise to effective adaptive immune response and immune memory, but can promote TGF-β production to inhibit Th1/Th2-mediated adaptive immune response, bind to CEACAM1 on the B cell surface to promote apoptosis in B cells, and combine with CEACAM1 on the T cell surface to inhibit helper T cell proliferation, which makes it difficult for B cells to produce high-affinity specific antibodies. With the increasing drug-resistance of NG, immunological studies may play a significant role in the development of novel therapies and effective vaccines against the infection.
Adaptive Immunity ; Antibodies ; immunology ; Antigens, CD ; immunology ; Cell Adhesion Molecules ; immunology ; Complement Factor H ; immunology ; Gonorrhea ; immunology ; Humans ; Immune Evasion ; immunology ; Immunity, Innate ; immunology ; Neisseria gonorrhoeae ; immunology

OBJECTIVETo study the effect of PF4 on the adherence of leukemic CD34+ KG1a cell to human umbilical vein endothelial cell line ECV-304 cell and on the expression of adhesive molecules.

METHODSAdhesion assay and adhesion blocking assay were respectively applied to measure the effect of PF4 and/or adhesion molecule monoclonal antibodies on the adhesion property of KG1a. The expressions of adhesion molecules were determined by RT-PCR and FACS analysis.

RESULTSThe adhesion of KG1a cells to ECV-304 was significantly enhanced in the presence of PF4. Such enhancement was also observed when KG1a or ECV-304 cells were separately treated with PF4 before interaction. The adhesion capacity of KG1a cells was reduced when cells were co-incubated with the blocking monoclonal antibodies (MoAbs) against CD49d, CD106, CD54, respectively. In contrast, MoAbs against CD62L, CD62P and CD62E had no such effect. During a period of 3 hours when KG1a or ECV-304 cells were respectively incubated with PF4, the mRNA expressions of CD49 d, CD54 were up-regulated. Furthermore, when KG1a or ECV-304 cells were incubated with PF4 for 2 hours, respectively, the percentages of CD49d+ KG1a cells and CD54+ ECV-304 were increased significantly.

CONCLUSIONPF4 can enhance KG1a cell adhesive capacity by increasing the expressions of adhesion molecules.

Antigens, CD34 ; metabolism ; Cell Adhesion ; drug effects ; Cell Adhesion Molecules ; metabolism ; Cell Line, Tumor ; Humans ; Leukemia, Myeloid, Acute ; immunology ; pathology ; Platelet Factor 4 ; pharmacology ; Umbilical Veins ; cytology

To verify the spectrum of CD99-expressing lymphoid malignancy, an immunohistochemical study for CD99 was carried out in 182 cases of non-Hodgkin's lymphoma, including 21 lymphoblastic lymphomas, 11 small lymphocytic lymphomas, 9 mantle cell lymphomas, 12 follicular lymphomas, 37 diffuse large B cell lymphomas, 18 Burkitt's lymphomas, 28 NK/T-cell lymphomas, 8 angioimmunoblastic T-cell lymphomas, 23 peripheral T-cell lymphomas, unspecified, and 15 systemic anaplastic large cell lymphomas. CD99 was positive in all T-lymphoblastic lymphomas and in 60% of B-lymphoblastic lymphomas. Majority of T and NK cell lymphomas were negative for CD99, except anaplastic large cell lymphomas (ALCLs). Eight of 15 cases (54%) of ALCLs reacted with anti CD99 antibody. Seven of 10 (70%) ALK positive ALCLs expressed CD99, whereas only 1 of 5 (20%) ALK negative ALCLs were positive. Of the mature B-cell lymphomas, 5.4% (2/37) of diffuse large B cell lymphomas and 11.1% (2/18) of Burkitt's lymphomas expressed CD99. In conclusion, CD99 is infrequently expressed in mature B and T cell lymphomas, except ALK-positive ALCL. High expression of CD99 in ALK-positive ALCL is unexpected finding and its biologic and clinical significances have yet to be clarified.
Antigens, CD/*metabolism ; Blotting, Western ; Cell Adhesion Molecules/*metabolism ; Humans ; Immunohistochemistry ; Lymphoma, Large-Cell/enzymology/*immunology/pathology ; Lymphoma, Non-Hodgkin/enzymology/*immunology/pathology ; Protein-Tyrosine Kinase/immunology/*metabolism

OBJECTIVETo study the clinical and pathologic characteristics of poorly differentiated cutaneous angiosarcoma of scalp.

METHODSEight cases of poorly differentiated cutaneous angiosarcoma of scalp were enrolled into this study. The clinical manifestations and histopathologic features were analyzed. Immunohistochemical study for CD31, CD34, factor VIII-related antigen, vimentin, AE1/AE3, CAM5. 2, epithelial membrane antigen and carcinoembryonic antigen was performed.

RESULTSThe mean age of the patients was 69 years. The male-to-female ratio was 5 : 3. The tumor manifested clinically as bruise-like lesion in early phase, indurated erythematous plaque accompanied by nodules, ulcerations and bleeding in advanced phase. Histologically, the tumor was composed of solid sheets of undifferentiated spindle cells which were not easily recognizable as vascular in origin. Nuclear atypia was always present. The tumor cells in all of the 8 cases strongly expressed CD31, factor VIII-related antigen and vimentin. Weak expression of CD34, AE1/AE3 and CAMS. 2 was noted in 2, 4 and 4 cases, respectively. The staining for epithelial membrane antigen, carcinoembryonic antigen and S-100 was negative. Conclusions Angiosarcoma needs to be excluded by histologic examination whenever bruise-like and erythematous lesions occurring on scalp skin of elderly patients. The endothelial origin of the tumor cells can be confirmed with immunostaining for CD31, CD34 and factor VIII-related antigen.

Aged ; Aged, 80 and over ; Antigens, CD34 ; immunology ; Biomarkers, Tumor ; analysis ; Cell Adhesion Molecules ; Cell Differentiation ; Endothelium ; metabolism ; Female ; Hemangiosarcoma ; immunology ; Humans ; Male ; Middle Aged ; Platelet Endothelial Cell Adhesion Molecule-1 ; immunology ; Scalp ; pathology ; Skin Neoplasms ; immunology ; metabolism ; pathology ; Vimentin ; analysis

We investigated the co-stimulatory role of a cell-surface protein, CD99. Co-ligation of CD99 and suboptimal CD3 induced T-cell activation to a level comparable to that obtained with optimal CD3 or CD3+CD28. We also noted concomitant enhancement of the earliest T-cell receptor (TCR) signaling events. In addition, co-ligation of CD99 and CD3 led to translocation of TCR complexes into the lipid raft, without concomitant migration of CD99 to the raft, and consequent enhancement of TCR zeta-mediated signal 1. These data demonstrate the unique properties of CD99 co-stimulation that distinguish this molecule from CD28 and other raft-resident co-stimulatory factors.
Antigens, CD/*immunology ; Antigens, CD3/immunology ; Cell Adhesion Molecules/*immunology ; Down-Regulation ; Humans ; Jurkat Cells ; Lymphocyte Activation/*immunology ; Membrane Microdomains/*immunology ; Membrane Proteins/*immunology ; Phosphorylation ; Phosphotyrosine/*metabolism ; Protein Transport ; Receptors, Antigen, T-Cell/*immunology ; T-Lymphocytes/*immunology

We investigated the expression of CD99 in 35 hyperplastic perigastric lymph nodes, which were resected for gastric carcinoma or chronic peptic ulcer. Essentially, all lymphocytes in lymph nodes expressed CD99, but there were two populations with respect to the intensity of CD99 expression--CD99high and CD99low cells. We showed CD99high cells were distributed in paracortical and medullary cords by immunohistochemical study while germinal center cells were CD99low. Using three-color flow cytometric analysis with CD3, CD4, CD8, CD19, CD23, CD45RA, CD45RO, CD69, CD138, IgM, IgD, and IgG, most of CD99high cells were shown to be activated/memory T cells. CD4+CD45RO+ T cells were the subset revealing the highest intensity of CD99 expression while CD4+CD45RA+ T cells were CD99low. Among B cells, IgG+ B cells revealed a higher level of CD99 molecules than IgM+ B cells. These results suggest that CD99 is one of activation-related molecules which are upregulated in recently activated lymphocytes.
Adult ; Aged ; Antigens, CD/analysis* ; B-Lymphocytes/immunology* ; Cell Adhesion Molecules/analysis* ; Flow Cytometry ; Germinal Center/immunology ; Human ; Immunohistochemistry ; Immunologic Memory/immunology* ; Lymph Nodes/immunology* ; Middle Age ; Peptic Ulcer/immunology* ; Stomach Neoplasms/immunology* ; T-Lymphocytes/immunology*

OBJECTIVETo study the effect of ex vivo expansion on the adhesion activities of umbilical cord blood hematopoietic stem and progenitor cells (HSPC).

METHODSFresh UCB CD(34)(+) cells were cultured in a serum and stroma-free culture system. At day 7, day 10 and day 14, CD(34)(+) cells were re-selected from the expanded products. The expression of adhesion molecules (CAMs) such as VLA-4, VLA-5, LFA-1, ICAM-1, HCAM, L-selectin and PECAM-1, and the adhesion activity of the expanded CD(34)(+) cells were evaluated and compared with those of precultured fresh CD(34)(+) cells.

RESULTS(1) The CD(34)(+) cells expressing homing-related CAMs were increased (from 15-fold increase for CD(34)(+) CD(54)(+) subset to 72-fold increase for CD(34)(+) CD(49e)(+) subset at day 14). (2) The expressions of CD(49d), CD(44), CD(11a) and CD(49e) on the expanded CD(34)(+) cells were increased or sustained the same levels as those on fresh UCB CD(34)(+) cells, while the expression of CD(62L), CD(54) and CD(31) on expanded CD(34)(+) cells declined with the cultivating. (3) Spontaneous adhesion and SDF-1-induced adhesion tended to be increased in the course of the first 10 day's culture.

CONCLUSIONSThe culture system used in this study could substantially support the expansion of HSPCs expressing the above CAMs, and the expanded HSPCs would sustain their intrinsic adhesion potentials.

Antigens, CD ; analysis ; Antigens, CD34 ; analysis ; Cell Adhesion ; Cell Adhesion Molecules ; biosynthesis ; Cell Division ; Fetal Blood ; cytology ; immunology ; metabolism ; Flow Cytometry ; Hematopoietic Stem Cells ; cytology ; immunology ; metabolism ; Humans ; Receptors, Lymphocyte Homing ; biosynthesis

CD99 plays an critical role in the diapedesis of monocytes, T cell differentiation, and the transport of MHC molecules. Engagement of CD99 by agonistic monoclonal antibodies has been reported to trigger multifactorial events including T cell activation as well as cell-cell adhesion during hematopoietic cell differentiation. In this study, to identify the functional domains participating in the cellular events, we mapped the epitopes of CD99, which are recognized by two agonistic CD99 monoclonal antibodies, DN16 and YG32. Using recombinant fusion proteins of GST with whole or parts of CD99, we found that both antibodies interact with CD99 molecules independently of sugar moieties. DN16 mAb detected a linear epitope located in the amino terminal region of CD99 while YG32 mAb bound another linear epitope in the center of the extracellular domain. To confirm that the identified epitopes of CD99 are actually recognized by the two mAbs, we showed the presence of physical interaction between the mAbs and the fusion proteins or synthetic peptides containing the corresponding epitopes using surface plasmon resonance analyses. The dissociation constants of DN16 and YG32 mAbs for the antigen were calculated as 1.27 X 10(-7) and 7.08 X 10(-9) M, respectively. These studies will help understand the functional domains and the subsequent signaling mechanism of CD99.
Amino Acid Sequence ; Antibodies, Monoclonal/*immunology ; Antigens, CD/*chemistry/*immunology ; Blotting, Western ; Cell Adhesion Molecules/*chemistry/*immunology ; *Epitope Mapping ; Epitopes/*chemistry/*immunology ; Glutathione Transferase ; Human ; Molecular Sequence Data ; Peptide Fragments/chemistry/immunology ; Recombinant Fusion Proteins/chemistry/immunology

Severe acute respiratory syndrome (SARS) has recently recognized as a new human infectious disease. A novel coronavirus was identified as the causative agent of SARS. This report summarizes the hematological findings in SARS patients and proposes a hypothesis for the pathophysiology of SARS coronavirus related abnormal hematopoiesis. Hematological changes in patients with SARS were common and included lymphopenia (68% - 90% of adults; 100% of children, n = 10), thrombocytopenia (20% - 45% of adults, 50% of children), and leukopenia (20% - 34% of adults, 70% of children). The possible mechanisms of this coronavirus on blood system may include (1) directly infect blood cells and bone marrow stromal cells via CD13 or CD66a; and/or (2) induce auto-antibodies and immune complexes to damage these cells. In addition, lung damage in SARS patients may also play a role on inducing thrombocytopenia by (1) increasing the consumption of platelets/megakaryocytes; and/or (2) reducing the production of platelets in the lungs. Since the most common hematological changes in SARS patients were lymphopenia and immunodeficiency. We postulate that hematopoietic growth factors such as G-CSF, by mobilizing endogenous blood stem cells and endogenous cytokines, could become a hematological treatment for SARS patients, which may enhance the immune system against these virus.
Adult ; Antigens, CD ; immunology ; Antigens, Differentiation ; immunology ; CD13 Antigens ; immunology ; Cell Adhesion Molecules ; Child ; Hematologic Diseases ; immunology ; physiopathology ; Hematopoiesis ; physiology ; Humans ; SARS Virus ; Severe Acute Respiratory Syndrome ; immunology ; physiopathology ; virology