Agents and Actions, vol. 31, 1/2 (1990) 0065-4299/90/020086-10 $1.50 + 0.20/0 9 1990 Birkh~iuser Verlag, Basel Phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophils in the presence of N-formimidoyl thienamycin A.B. Rodriguez 1, C. Barriga 1 and M. de la Fuente 2 1 Department of Physiology, Faculty of Science, University of Extremadura, 06071 Badajoz, Spain 2 Department of Animal Biology II, (Animal Physiology), Faculty of Biological Science, Complutense University, 28040 Madrid, Spain Abstract The efficacy of an antibiotic in the treatment of bacterial infections depends upon the interactions of the drug, bacteria and phagocytes. We have studied "in vitro" the effect of N-formimidoyl thienamycin (Imipenem), a novel fi-lactamic antibiotic, on the phagocytic function and antibody-dependent cellular cytotoxicity of human neutrophil leukocytes. The incubation of these cells with 50 gg/ml of Imipenem similar to the therapeutic levels reached in plasma results in an increase of their adherence capacity to nylon fiber and to substrate, induced mobility or chemotaxis, opsonization, phagocytosis of Candida albicans (with serum, with decomplementarized serum and without serum) and latex beads, candidicidal power and the capacity of NBT reduction. Imipenem at this dose also presents chemoattractant power for neutrophils and enhances the antibody-dependent cellular cytotoxicity (ADCC). Introduction Neutrophil polymorphonuclear leukocytes (PMNns) are responsible for the nonspecific im- mune response of the host to inflammatory and infectious processes [1]. These cells are capable of adhering to blood vessel walls and subsequently reaching the damaged tissues by means of dia- pedesis and chemotaxis. Once at the site of infec- tion, these cells adhere to the pathogen (opsoniza- tion), phagocytizing and destroying them internal- ly, aided by the enzymes contained in their lyso- somes [2]. Inhibition of any of these steps before phagocytosis can be expected to reduce host de- fence against bacterial invasion. Indeed, several different defects in granulocytic function have been documented in patients with recurrent infec- Address correspondence to: Dr. A. B. Rodriguez, Department of Physiology, Faculty of Science, University of Extremadura, Avda. de Elvas s/n, 06071 Badajoz, Spain. tions [3]. On the other hand, stimulation of the function of these cells represents an improved capacity of response to infections on the part of the host. Cellular cytotoxicity is a leukocyte mediated extra- cellular killing mechanism. There are several types of cytotoxicity including major histocompatibility complex (MHC) antigen-restricted T cell cytotox- icity, natural killer cytotoxicity (NKC) [4], and antibody-dependent cellular cytotoxicity (ADCC). The latter type is the one carried out by poly- morphonuclear leukocytes [5], which includes target recognition, binding, programming to kill, effector cell-independent target cell lysis, and effec- tor cell recycling [6, 7]. Imipenem or N-formimidoyl thienamycin (MK- 0787), a new carbapenem antibiotic with an unusu- ally broad spectrum of activity against Gram-pos- itive and Gram-negative bacteria including Pseu- domonas aeruginosa [8, 9] which is also stable in