Page 170 - Hematology_ Basic Principles and Practice ( PDFDrive )
P. 170

128    Part II  Cellular Basis of Hematology


                                                                            V
                                                          NH 2               NH 2  Hyaluronan-     Carbohydrate-
                                                                                                    recognition
                                                                                     binding
                                                             Ib α                    domain          domain
                                                                                      S S
                                         NH
                    Ligand-binding          2                                         S S                   NH 2
                       region
                 α IIb        β 3                                                     S S
                   Ca 2+                                          Ib  IX                  NH 2
                   Ca 2+                      lg-like              β
                   Ca 2+                      domains             NH  NH
                   Ca 2+         Cysteine                           2   2                  Site for
          Heavy chain  NH 2  NH 2  rich        O-linked                                    alternative
                                                                                           splicing of
                                 repeats
          Light chain                           glycans      S S                           exons




                 COOH      COOH         COOH             COOH     COOH    COOH       COOH             COOH
                 Integrin               lg-like                  GPIb/IX/V           CD44            P-selectin
                 (α β )                receptor                   complex
                   IIb 3
                                      (VCAM) -1
                        Fig. 12.1  SCHEMATIC DIAGRAMS OF SEVERAL TYPES OF CELL SURFACE ADHESION RECEP-
                        TORS.  Integrins  consist  of  noncovalently  linked  α-  and  β-subunits,  both  of  which  contribute  to  ligand
                        binding. The platelet αIIbβ3 integrin is illustrated at far left. Ig-like receptors contain a variable number of
                        Ig homology domains, of which some bind ligands and others extend the ligand-binding domains from the
                        membrane. Shown second from left is VCAM-1, which contains seven Ig domains; the two domains that bind
                        to integrins are shaded. The platelet GPIb–IX–V complex, depicted in the middle diagram, consists of several
                        leucine-rich protein subunits. CD44, illustrated next, contains an amino-terminal (N-terminal) domain that
                        binds to hyaluronan. Each of the selectins contains an N-terminal carbohydrate recognition domain that binds
                        sialylated  and  fucosylated  oligosaccharides  on  specific  cell-surface  GP  ligands.  Illustrated  at  far  right  is
                        P-selectin, the largest of the three selectins. GP, Glycoprotein; Ig, immunoglobulin; VCAM-1, vascular cell
                        adhesion molecule-1.

          TABLE   Integrins on Blood Cells
          12.1
         Integrin 
         Designation  Other Name(s)    Expressed by               Ligand(s)                Function(s)
         α 1 β 1   VLA-1               Leukocytes, other cells    Collagens, LM            Adhesion to ECM
         α 2 β 1   VLA-2 GPla/lla      Leukocytes, platelets, other cells  Collagens, LM   Adhesion to ECM
                   VLA-3               Leukocytes, other cells    Collagens, LM, FN        Adhesion to ECM
         α 3 β 1
                   VLA-4               Monocytes, lymphocytes, eosinophils  VCAM-1, FN     Adhesion to cells, ECM
         α 4 β 1
                   VLA-5 GPlc/lla      Leukocytes, platelets, other cells  FN              Adhesion to ECM
         α 5 β 1
                   VLA-6 GPlc/lla      Leukocytes, platelets, other cells  LM              Adhesion to ECM
         α 6 β 1
                                       Neutrophils                VCAM-1                   Adhesion to ECs
         α 9 β 1
                   LFA-1 CD11a/CD18    Leukocytes                 ICAM-1, -2, -3           Leukocyte aggregation and
         α L β 2
                                                                                             adhesion
                   MAC-1 CR3 CD11b/CD18  Neutrophils, monocytes   ICAM-1, FIB, CR for iC3b  Neutrophil aggregation and
         α M β 2
                                                                                             adhesion to ECs
                   P150,95 CD11c/CD18  Neutrophils, monocytes     CR for iC3b              Adhesion to ECs
         α X β 2
                   CD11d/CD18          Eosinophils, monocytes, lymphocytes  VCAM-1, ICAM-3  Adhesion to leukocytes and to
         α D β 2
                                                                                             ECs
                   GPllb/llla          Platelets                  FIB, FN, vWF, VN, TSP    Platelet adhesion and
         α IIb β 3
                                                                                             aggregation
                   VN receptor         Platelets, ECs             FIB, FN, vWF, VN, TSP, collagens  Platelet adhesion, angiogenesis
         α V β 3
         α 4 β 7   LPAM-1              Lymphocytes                VCAM-1, MAdCAM-1, FN     Lymphocyte adhesion to ECs
                                                                                             and ECM
         CR, Complement receptor; EC, endothelial cell; ECM, extracellular matrix; FIB, fibrinogen; FN, fibronectin; GP, glycoprotein; LFA-1, leukocyte function-associated antigen;
         LM, laminin; LPAM-1, lymphocyte Peyer patch adhesion molecule; MAdCAM-1, mucosal addressin cell adhesion molecule-1; TSP, thrombospondin; VCAM-1, vascular
         cell adhesion molecule-1; VLA, very late-appearing antigen; VN, vitronectin; vWF, von Willebrand factor.
   165   166   167   168   169   170   171   172   173   174   175