Neuropeptides and their peptidases: edited by A.J. Turner. VCH, Weinheim, Vol. 1, 1987, pp. 295, DM 156, US$ 93.50

Abstract

CD10 (common acute lymphoblastic leukemiaantigen, CALLA) is a 100 kDa cell surface glycoprotein (Brown et al., 1975; Ritz et al., 1980; Metzgar et al., 1981; Cossman et al., 1983; Graves et al., 1983; Shipp et al., 1988, 1989), expressed by acute lymphoblastic leukemias (Brown et al., 1975; Ritz et al., 1980), normal lymphoid progenitors (Greaves et al., 1983), mature polymorphonuclear leukocytes (Cossman et al., 1983) and certain non-hematopoietic cells (Metzgar et al., 1981). Molecular cloning and expression studies have shown that CD10 is the zinc metalloprotease, neutral endopeptidase 24.11 (NEP, “enkephalinase”) (LeTarte et al., 1988; Shipp et al., 1988, 1989). CD 10/NEP hydrolyzes a number of naturally occurring peptides including the endogenous opioid pentapeptides met- and leu- enkephalin. Hence, the enzyme in brain has been termed “enkephalinase” (Malfroy et al., 1978). In invertebrate organisms such as the mollusc M. edulis, met-enkephalin triggers inflammatory responses by inducing morphological changes, directed migration, and aggregation of hemocytes (Stefano et al., 1989a,b). We recently found that M. edulis hemocytes express a CD10/NEP related structure and that abrogation of CD10/NEP enzymatic activity reduces the amount of met-enkephalin required for hemocyte activation by five orders of magnitude (Shipp et al., 1990). Human CD 10+ polymorphonu clear leukocytes are similarly responsive to met-enkephalin and inhibition of CD 10/NEP enzymatic activity dramatically potentiates met-enkephalin effects in these cells (Shipp et al., 1990). Therefore, CD10/NEP related structures modulate enkephalin-mediated inflammatory responses in organisms that are ≈500 million years divergent in evolution (Meglitsch, 1967). These results suggest that in hematopoietic, and perhaps other cells, enkephalin signals are regulated via co-expression of cell surface opioid receptors and the CD10/NEP hydrolytic enzyme and hat CD10/NEP functions to down-regulate induced responses to peptide hormones that are CD10/NEP substrates.