DEVELOPMENT OF MACROPHAGE ANTICRYPTOCOCCAL ACTIVITY IN-VITRO IS DEPENDENT ON ENDOGENOUS M-CSF

We previously showed that nonactivated resident murine peritoneal macr ophages (PM) from five strains (e.g., BALB/c) have C'-dependent fungis tasis for Cryptococcus neoformans in 24-h coculture, but not CD-1 PM u nless culture time was extended or M-CSF treatment was used. We studie d effect of a rat IgG, monoclonal (m) antibody (Ab) to murine M-CSF re ceptor on this anticryptococal activity. Culture of BALB/c PM with mAb , diluted 1:10, prechallenge reduced fungistasis from 58 to 21% (P < 0 .01), whereas further 10-fold dilutions did not. Moreover, M-CSF pretr eatment (5000 U/ml) significantly enhanced fungistasis (to 85%), where as adding mAb 1:10 or 1:100 reduced that (to 58 and 77%, respectively, P < 0.01). In 48-h culture CD-1 PM had 39% fungistasis, reduced to 0% by mAb, RI-CSF treatment of CD-1 PM increased fungistasis to 72%, whi ch was reduced to 13 or 58% (P < 0.001) by 1:10 or 1:100 mAb, respecti vely. Complete blocking by mAb of CD-1 PM activity was consistent with lack of measurable early endogenous CD-1 M-CSF production. Increasing exogenous M-CSF could overcome the inhibition by mAb (64% fungistasis BALB/c PM reduced to 11% with inhibition by mAb or increased to 94% w ith 5000 U/ml M-CSF; 37% with both mAb and M-CSF, 51% with mAb and 10, 000 U/ml; P < 0.05, 5000 U/ml + mAb vs 10,000 U/ml + mAb). Moreover, r abbit Ab to M-CSF significantly reduced anticryptococcal activity of u ntreated BALB/c macrophages, In summary, development of PM fugistatic activity is dependent on endogenous M-CSF, since it is blocked by anti -receptor mAb (as is exogenous M-CSF stimulation) or anti-M-CSF Ab, an d macrophages of the mouse strain with delayed activity had no measura ble early IM-CSF production. (C) 1998 Academic Press.