ACTION AND TARGET-CELL SPECIFICITY OF HUMAN MACROPHAGE-STIMULATING PROTEIN (MSP)

Macrophage-stimulating protein (MSP) induces mouse resident peritoneal macrophages to become responsive to the chemoattractant C5a and to in gest C3bi-coated erythrocytes. We now show that MSP action is not limi ted to complement-induced responses, because it also induced responsiv eness to the noncomplement chemoattractant casein. In addition to stim ulating responsiveness to attractants, MSP functioned alone as a chemo attractant for resident peritoneal macrophages, with an optimal concen tration of approximately 0.2 nM. A critical difference between MSP and C5a is that resident macrophages did not migrate to C5a without an ad ditional stimulus such as MSP in the cell suspension, whereas macropha ges suspended in medium alone migrated to MSP in the attractant well. Thus, in contrast to C5a, MSP seems capable of a dual role, both activ ator and attractant. MSP had no effect on responsiveness of mouse peri toneal exudate macrophages to C5a; nor could it attract exudate macrop hages or human blood monocytes. Absorption studies showed that residen t macrophages have a receptor for MSP, but exudate macrophages do not. In view of these findings, it seems that the biological role of MSP i s not as a recruiter of blood monocytes to sites of inflammation, but as an activator of mature macrophages. The MSP-induced activated state for responsiveness to C5a or C3bi was transient, and decayed at a fir st order rate with a t1/2 of approximately 1 h. This is a new example of the transience of activation induced in macrophages by proinflammat ory stimuli.