Development of macrophage anticryptococcal activity in vitro is dependent on endogenous M-CSF.
We previously showed that nonactivated resident murine peritoneal macrophages (PM) from five strains (e.g., BALB/c) have C'-dependent fungistasis for Cryptococcus neoformans in 24-h coculture, but not CD-1 PM unless culture time was extended or M-CSF treatment was used. We studied effect of a rat IgG1 monoclonal (m) antibody (Ab) to murine M-CSF receptor 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 pretreatment (5000 U/ml) significantly enhanced fungistasis (to 85%), whereas 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, M-CSF treatment of CD-1 PM increased fungistasis to 72%, which was reduced to 13 or 58% (P < 0. 001) by 1:10 or 1:100 mAb, respectively. 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% with 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, rabbit Ab to M-CSF significantly reduced anticryptococcal activity of untreated 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, and macrophages of the mouse strain with delayed activity had no measurable early M-CSF production.
Brummer
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Department of Medicine, Santa Clara Valley Medical Center, and California Institute for Medical Research, San Jose, California, 95128, USA.
Gilmore
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GL
Shadduck
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RK
Stevens
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DA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D003455:Cryptococcus neoformans / Q000276:immunology*; D008262:Macrophage Activation; D016173:Macrophage Colony-Stimulating Factor / Q000502:physiology*; D008264:Macrophages / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D011817:Rabbits; D051381:Rats; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000502:physiology
D000911:Antibodies, Monoclonal; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor