Pablo Engel

The selectins: vascular adhesion molecules.

The selectin family of adhesion molecules mediates the initial attachment of leukocytes to venular endothelial cells before their firm adhesion and diapedesis at sites of tissue injury and inflammation. The selectin family consists of three closely related cell‐surface molecules with differential expression by leukocytes (L‐eelectin), platelets (P‐se‐lectin), and vascular endothelium (E‐ and P‐selectin). The selecting have characteristic extracellular regions composed of an amino‐terminal lectin domain that binds a carbohydrate ligand, an epidermal growth factor‐like domain, and two to nine short repeat units homologous to domains found in complement binding proteins. In contrast to most other adhesion molecules, selectin function is restricted to leukocyte interactions with vascular endothelium. Multiple studies indicate that the selectins mediate neutrophil, monocyte, and lymphocyte rolling along the venular wall. The generation of selectin—deficient mice has confirmed these findings and provided further insight into how the overlapping functions of these receptors regulate inflammatory processes. Se‐ lectin‐directed therapeutic agents are now proven to be effective in blocking many of the pathological effects resulting from leukocyte entry into sites of inflammation. Future studies are focused on how the selectins interact with the increasing array of other adhesion molecules and inflammatory mediators.—Tedder, T. F., Steeber, D. A., Chen, A., Engel, P. The selectins: vascular adhesion molecules. FASEB J. 9, 866‐873 (1995)

Abnormal B lymphocyte delevopment, activation, and differentiation in mice that lack or overexpress the CD19 signal transduction molecule

CD19-deficient mice were generated to examine the role of CD19 in B cell growth regulation in vivo. Deletion of CD19 had no deleterious effects on the generation of B cells in the bone marrow, but there was a significant reduction in the number of B cells in peripheral lymphoid tissues. B cells from CD19-deficient mice exhibited markedly decreased proliferative responses to mitogens, and serum immunoglobulin levels were also significantly decreased. In contrast, mice that overexpressed CD19 had significant defects in early B cell development in the bone marrow, augmented mitogenic responses, and increased serum immunoglobulin levels. These experiments indicate that CD19 functions to define signaling thresholds for cell surface receptors that regulate B lymphocyte selection, activation, and differentiation.

The CD19/CD21 signal transduction complex of B lymphocytes

CD19 and CD21 are B-cell surface molecules that associate with each other and with CD81 and Leu-13 to generate a signal transduction complex that is independent of the antigen receptor. Current studies, reviewed here by Thomas Tedder, Liang-Ji Zhou and Pablo Engel, indicate an important biological role for this protein complex in the regulation of B-cell development and activation.

New CD from the B cell section of the Fifth International Workshop on Human Leukocyte Differentiation Antigens.

This review summaries the expression and the molecular and biochemical characteristics of eight new Clusters of Differentiation (CD79-CD86) established by the B cell Section during the Fifth International Workshop on Human Leukocyte Differentiation Antigens. CD79 monoclonal antibodies (mAb) identify the mbl (CD79 alpha) and B29 (CD79 beta) components of the surface immunoglobulin (Ig) receptor complex. CD80 (B7/BB-1) is a costimulatory molecule that serves as the ligand for two molecules expressed on T lymphocytes, CD28 and CTLA-4. CD81 (TAPA-1) and CD82 (R2) are new members of the tetra-spans family of transmembrane proteins, which include CD9, CD37, CD53 and CD63. These proteins are postulated to be involved in signal transduction. CD83 (HB15) is a marker for human interdigitating reticulum cells, circulating dendritic cells and Langerhans cells. CDw84 and CD85 are new B cell-associated molecules that are also expressed by monocytes. CD86 is a new B cell activation antigen.

L-Selectin Regulation of Lymphocyte Homing and Leukocyte Rolling and Migration

The recruitment of leukocytes from the blood and lymphatic vascular systems and their extravasation into tissues is critical for host defense against pathogens and response to tissue injury and also contributes to the pathophysiology of many inflammatory diseases. This process is regulated in part by specific leukocyte-endothelial cell interactions with several families of cell adhesion molecules participating in recognition, adhesion, and extravasationl. The selectin family of adhesion molecules mediates the initial interactions of leukocytes with endothelium that allows leukocytes to roll along the venular wa112,3. The selectins bind to sialomucins which serve as scaffolds for the proper presentation of carbohydrate ligands to the selectins. Subsequently, integrins and immunoglobulin superfamily members interact to arrest leukocyte rolling and mediate “firm” attachment to the vascular endothelium. Multiple leukocyte integrins are known to be involved including LFA-1 (CD11a/CD18), Mo-1/Mac-1 (CD11b/CD18), VLA-4 (CD49d/CD29) and perhaps p150/95 (CD11c/CD18). Several members of the Ig superfamily such as Vascular Cell Adhesion Molecule-1 (VCAM-1, CD106), Intercellular Adhesion Molecule-1 (ICAM-1, CD54), ICAM-2 (CD102) and ICAM-3 (CD50) serve as integrin ligands. The utilization of different selectin, integrin, and immunoglobulin superfamily members by various leukocyte subclasses as they pass through distinct beds of vascular endothelium allows for considerable diversity and specificity in leukocyte migration4. L-selectin is a member of the selectin family of adhesion receptors and plays a central role in governing the migration patterns of different leukocyte classes5,6.