The Effect of Hybridoma Antibody Administration upon Neutrophil Kinetics during Experimental Type III Group B Streptococcal Sepsis

Abstract

Summary: Groups of newborn rats were transthoracically inoculated with 1 × 10⁶ type III group B streptococci/g body wt, either alone or in combination with 1.5 microgram/g body wt of type-specific antibody derived fom hybridoma cell lines. Ninety-four percent of the animals who received bacteria alone died. In contrast, none of those treated with antibody died (P < 0.005). Kinetic studies suggested that antibody may have offered protection, in part, by facilitating the neutrophil response. Animals who received only bacteria exhibited a marked neutropenia (20 ± 18/mm³, mean ± S.E.M.) whereas infected animals treated with antibody did not (3800 ± 30/mm³, P < 0.001). Furthermore, within 2 h of inoculation, antibody-treated animals mobilized stored neutrophils, whereas significant neutrophil mobilization did not occur in the animals which received bacteria alone until 6 h. In the animals receiving bacteria alone, exhaustion of the neutrophil supply quickly occurred (remaining storage neutrophils at 6 h, 0.2 ± 0.1 × 10⁶ cells). In contrast, animals, which received antibody, maintained an adequate supply of stored neutrophils (7.0 ± 0.4 × 10⁶ P < 0.001). The migration of neutrophils to the site of inoculation was measured by assaying the lungs' content of myeloperoxidase, a marker enzyme for granulocytes. The right and left lungs of animals not receiving antibody accumulated the same quantity of neutrophils, with peak pulmonary neutrophil accumulation occurring 6 h after the infection. In antibody recipients, however, the inoculated lung accumulated significantly more neutrophils than the opposite lung and peak pulmonary neutrophil accumulation occurred at 2 rather than 6 h.

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