Mechanisms of the adjuvant effect of hemoglobin in experimental peritonitis. V. The significance of the coordinated iron component.

Adjuvant effects of hemoglobin, methemoglobin, hematin, and ferric nitrilotriacetate (FENTA) on the lethality of E. coli peritonitis in rats were compared. The functional importance of coordinated iron was affirmed by the findings that: (1) hematin simulated the hemoglobin effect when administered on an iron-equivalent basis and (2) hematoporphyrin was inactive at the same levels as hematin. The effects of hemoglobin and methemoglobin were virtually identical, suggesting that the oxidation state of the metallic center is immaterial, and analyses of peritoneal contents during lethal peritonitis promoted by either adjuvant revealed insignificant interconversions of these compounds. Saturation of systemic iron-binding capacity could not be detected during lethal E. coli--hemoglobin peritonitis and deliberate saturation of systemic transferrin by infusions of intravenous FENTA did not enhance the adjuvant effect of hemoglobin. The adjuvant effect of intraperitoneally administered FENTA was effectively nullified by simultaneous intraperitoneal deferoxamine injection, but the same maneuver had no effect on hemoglobin potency. Thus the adjuvant effect of hemoglobin in experimental peritonitis is functionally dependent on the iron component but cannot be explained by a non-heme iron flux. These characteristics suggest that adverse interactions of coordinated iron species with host defense chemistry will be fruitful subjects for future study.