Abstract. Human neutrophils (PMN) express a heterodimeric receptor that has ligand binding specificity for the Arg-Gly-Asp (RGD) sequence within many adhesive proteins. A monoclonal antibody, B6H12, which binds to this receptor, inhibits both RGDmediated ligand binding and stimulation of IgGmediated phagocytosis by fibronectin, fibrinogen, vitronectin, yon Willebrand's factor, and collagen type IV. By several criteria this receptor is neither a known very late antigen, a known cytoadhesin (gp IIb/IIIavitronectin receptor), nor a member of the LFA-1, Mac-l, p150,95 group of integrin receptors. Ligand binding via this receptor is rapidly inactivated by products of the myeloperoxidase-hydrogen peroxidehalide system of PMN. We conclude that this receptor, for which we propose the name leukocyte response integrin, is a signal-transducing molecule on PMN which may have a significant early role in modulation of PMN function at inflammatory sites.T HE integrin superfamily of adhesive receptors are transmembrane heterodimeric molecules which function in cell-matrix and cell-cell adhesion (Hynes, 1987). They are thought to function in adhesion processes by serving as transmembrane links between the extracellular environment and the cytoskeleton (Ruoslahti and Pierschbacher, 1987;Buck, 1987). As such they are intimately involved in many complex cell processes including thrombosis, hemostasis, cell maturation, embryogenesis, lymphocyte killing, and phagocytosis. The integrins can be roughly classified into three groups: (a) the very late antigens (VLAs) ~ first described on T lymphocytes, including the fibronectin (Fn) receptor from human placenta and osteosarcoma cells (Hemler et al., 1987); (b) cytoadhesins, including the platelet gp IIb/IIIa and the vitronectin receptor (VnR) (Ginsberg et al., 1988); and (c) LFA-1, Mac-l, p150,95, leukocyte-specific adhesion receptors, including the complement receptor for C3bi (CR3) . The heterodimers in each group are comprised of distinct alpha chains noncovalently linked to a common beta chain. Because of this, monoclonal antibodies to the beta chain of each group can be used to classify new receptors as members of one or another group within the integrins. As an example, the Fn receptor was shown to be a member of the VLA group be- cause it bound A-1A5, a monoclonal antibody which recognizes all VLA beta chains.In addition to significant structural and sequence homology, the integrins also exhibit ligand-binding similarities. Several of these receptors were first discovered because of their binding to extracellular matrix proteins via an Arg-GlyAsp (RGD) sequence in the matrix ligands. Our laboratory has recently characterized the RGD-binding proteins of human neutrophils (PMN) and monocytes by affinity chromatography of cell lysates on RGD-Sepharose (Brown and Goodwin, 1988). We showed that both phagocytes express a heterodimeric receptor distinct from the LFA-1, Mac-l, p150,95 family which exhibits immunological cross-reactivity with gp IIb/IIIa on platelets. Phagocytes undergo a ...

We have defined the cell surface molecules of human monocytes and PMN that bind to the chymotryptic cell binding domain of Fn and to a synthetic peptide, KYAVTGRGDS, based on the sequence of Fn, by affinity chromatography. Monocytes express two receptors that differ in their affinity for CBD-Sepharose and peptide-Sepharose, but that both recognize the RGD sequence. Only a single receptor is purified from PMN, which resembles the monocyte surface molecule that binds to peptide-Sepharose. These receptors are not part of the Mac-1, LFA-1, p(150,95) family, but do have homology to the platelet Fn receptor, gpIIb/IIIa. Interestingly, the antigenic crossreactivity between gpIIb/IIIa and the phagocyte receptors purified on peptide-Sepharose is largely in the beta chain of the receptors. The alpha chains appear to be distinct, based on molecular weight, antigenic analysis, and ligand specificity. This receptor also seems to be the surface molecule on monocytes that is critical for phagocytosis enhancement by Fn. Thus, we have defined the phagocyte Fn receptor that transduces the signal for increased phagocytosis by monocytes; it may be a third member of a family of adhesion molecules that includes the gpIIb/IIIa of platelets and the vitronectin receptor of fibroblasts.

Level IV-retrospective case series.

No abstract

Cardiovascular effects are identifiable in childhood even in mild forms of OI. Aortic dilation was the predominant finding, while valvular abnormalities were infrequent. Patients with more severe skeletal pathology (types 3/4) have more significant findings. Aortic and LV dilation in type 1 vs type 3/4 appears to differ based on the biochemical mechanism of disease.