Surface membrane heterogeneity among human mononuclear phagocytes

Abstract

Considerable information has been accumulated about the functional and metabolic differences that exist among human mononuclear phagocytes isolated from different anatomic sites. This heterogeneity may reflect the influence of environmental factors that stimulate circulating monocytes to differentiate in a distinctive manner, or may suggest the existence of predetermined subsets of macrophage precursors. The present study was designed to evaluate macrophage diversity at the membrane level by defining the expression of antigenic determinants on the surface of these cells. The expression of two new membrane differentiation antigens, BMM1 and PAM1, and of Mo1 and Mo2 were evaluated on blood monocytes, macrophages derived from cultured monocytes, breast milk macrophages (BMM), pulmonary alveolar macrophages (PAM), and peritoneal macrophages. Anti-BMM1 is a mouse IgG2a monoclonal antibody obtained by immunization with breast milk cells that recognizes an antigen expressed only on BMM but not on blood monocytes (or any other circulating cells), PAM, and peritoneal macrophages. BMM1 expression is also seen on HL60 promyelocytes induced toward macrophage differentiation by lymphokines but not by phorbol diester. Anti-PAM1, an IgG1 monoclonal antibody raised by immunization with PAM, reacts with an antigen found only on PAM. Blood monocytes, BMM, and peritoneal macrophages all share the previously described differentiation antigens, Mo1 and Mo2 (as well as Ia), whereas these markers are not found on PAM. BMM1 is associated with a two subunit surface protein of 46 and 40 Kd, and PAM1 resides on a 200 Kd polypeptide. The appearance of new antigens during differentiation (BMM1 on milk macrophages and PAM1 on PAM) and the disappearance of antigens more common to the macrophage lineage (absence of Mo1 and Mo2 on alveolar macrophages) indicate a significant heterogeneity at the membrane level among phagocytes obtained from different anatomic sites (but arising from a common myeloid precursor). The functional relevance of these structures selectively expressed by BMM and PAM is the object of further investigation.