Cardiorespiratory dysfunction in sepsis may be mediated by circulating complement, activated leukocytes, prostaglandins, or by a direct effect of endotoxin. The purposes of this study were to determine if pathogenic microbes produce these substances and to evaluate the direct effects of substances released by micro-organisms on granulocyte aggregation (GA). Escherichia coli, (E. coli), Aeromonas hydrophila (Aeromonas h.), Staphylococcus aureus (S. aureus), and Candida albicans, (Candida a.) were incubated in broth to a concentration of 10(9)/ml. Broth was filtered and analyzed by radioimmunoassay for complement components C3a and C5a, thromboxane B2 (TxB), and prostaglandin 6-keto-F1 alpha (PGI) and by the limulus amebocyte lysate test (LAL) for endotoxin. GA, % of maximum zymosan activated aggregation (% max. T), was performed with broth, microbial filtrates, and endotoxin or normal purified human leukocytes in HBSS. Organisms were incubated in broth (B), broth + 0.0135 mg/ml arachidonic acid (BA), and broth + arachidonic acid + indomethacin (BAI). Broth alone was the control (C).
Results: C3a, C5a, TxB, and PGI were not detectable in C broth or in any microbian filtrate. LAL was positive in all filtrates, but negative in C broth. GA responses were significantly greater in E. coli (56 +/- 5% max T) and Aeromonas h. (57% +/- 8% max T) compared to S. aureus (10 +/- 5% max T), Candida a. (14 +/- 8% max T) and C broth (1 +/- 1% max T). GA with purified E. coli endotoxin at concentrations measured in the filtrates was not related to the GA responses the original filtrates.(ABSTRACT TRUNCATED AT 250 WORDS)