REGULATION OF SECRETION AND SURFACE EXPRESSION OF MAC-2, A GALACTOSIDE-BINDING PROTEIN OF MACROPHAGES

Mac-2, a 30-35-kDa galactoside-binding protein, is synthesized at simi lar levels in murine peritoneal exudate macrophages whether recruited in response to an intraperitoneal pathogen Mycobacterium microti, to s terile inflammatory stimuli such as thioglycollate broth, or to concan avalin A. In elicited or activated macrophages up to 30% of Mac-2 is c onstitutively secreted, and secretion is stimulated markedly by calciu m ionophore A23187. Only thioglycollate elicited macrophages express c ell surface Mac-2, and binding is mostly (>80%) a result of affinity f or cell surface carbohydrate structures. Mac-2 surface expression is m arkedly reduced upon further activation of thioglycollate elicited mac rophages with bacterial lipopolysaccharide in vitro. Polylactosamine s tructures are present on all macrophage populations examined as determ ined by binding of Lycopersicon esculentum lectin, whereas alpha-galac tosyl residues detected by Griffonia simplicifolia isolectin B4 are ex pressed only on the thioglycollate elicited macrophages, indicating th at these residues are the major determinants responsible for Mac-2 sur face expression. Chemical crosslinking experiments have identified bin ding of endogenous cell-surface Mac-2 to three glycoproteins of molecu lar masses of 92, 125, and 180 kDa containing alpha-galactosyl and pol ylactosamine structures on thioglycollate-elicited macrophages. The re stricted cell surface distribution of Mac-2 on thioglycollate-elicited peritoneal macrophages, a population of recently recruited monocytes, suggests a role(s) in early events of macrophage infiltration and tis sue fixation such as extravasion and cell-matrix interactions.