Suppression of human neutrophil functions by tetracyclines.
Tetracycline inhibition of neutrophil-associated collagenolysis has been the focus of a number of investigations. Evidence has suggested that this inhibition results from the ability of this family of antimicrobial drugs to bind divalent cations such as Ca2+ and Zn2+, two cations that are required for full expression of activity of metalloproteinases such as collagenase and gelatinase. Data presented in this study demonstrate that tetracyclines can also inhibit neutrophil-mediated RBC lysis, superoxide anion synthesis, degranulation and migration. To some extent, tetracycline inhibition of neutrophil functions is mimicked by the Ca2+ binding agents, EDTA and TMB-8. However, Ca2+ enrichment restored full function to EDTA- and TMB-8-treated cells but not to tetracycline-treated neutrophils. This suggests that Ca2+ binding plays a role but is not the critical effect leading to tetracycline suppression of neutrophil functions. It has been suggested that tetracyclines can suppress leukocyte-associated tissue damage. Host tissues are protected from neutrophil-mediated damage by two mechanisms: 1. Neutrophil granule-associated enzymes are secreted in an inactive state; and, 2. tissues are protected from these enzymes by a potent inhibitor shield. Neutrophils can bypass these protective elements by activating enzymes and by destroying the shield through the synthesis of oxygen radicals. Therefore, tetracyclines may suppress neutrophil-mediated tissue damage by inhibiting their migration and degranulation and, potentially more importantly, by suppressing synthesis of oxygen radicals.(ABSTRACT TRUNCATED AT 250 WORDS)
Gabler
W L
WL
Department of Biochemistry, School of Dentistry, Oregon Health Sciences University, Portland.
Creamer
H R
HR
D000328:Adult; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects; D002464:Cell Migration Inhibition; D004318:Doxycycline / Q000494:pharmacology; D004910:Erythrocyte Membrane; D004912:Erythrocytes / Q000502:physiology; D006801:Humans; D008875:Middle Aged; D008911:Minocycline / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects*; D010118:Oxytetracycline / Q000494:pharmacology; D013481:Superoxides / Q000097:blood; D013752:Tetracycline / Q000494:pharmacology*
D013481:Superoxides; D013752:Tetracycline; D008911:Minocycline; D004318:Doxycycline; D002118:Calcium; D010118:Oxytetracycline