Augmentation of mast cell bactericidal activity by the anti-leukemic drug, 4-(3'bromo-4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline.
Mast cells play a pivotal role in host innate immune defense against gram negative bacterial infections by killing gram negative bacteria and recruiting neutrophils to the sites of active infection through the release of TNFalpha and leukotrienes. Here, we report that the anti-leukemic compound 4-(3'bromo-4'-hydroxylphenyl)-amino-6,7-dimethoxyquinazoline, designated as MASTPROM, augments the bactericidal activity of mast cells by increasing the binding of bacteria to and their phagocytosis by mast cells. MASTPROM also promoted the bacterial clearance in a mouse model of bacterial peritonitis. MASTPROM may provide the basis for novel supportive care regimens aimed at augmenting the bactericidal activity of mast cells and thereby potentiating the innate immune response against gram negative organisms.
Malaviya
Ravi
R
Department of Allergy and Inflammatory Diseases, Parker Hughes Cancer Center, St. Paul, MN 55113, USA.
Navara
Christopher
C
Uckun
Fatih M
FM
D000276:Adjuvants, Immunologic / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli; D004927:Escherichia coli Infections / Q000188:drug therapy; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D010538:Peritonitis / Q000188:drug therapy / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology* / Q000627:therapeutic use; D013047:Specific Pathogen-Free Organisms
D000276:Adjuvants, Immunologic; D011799:Quinazolines; C113888:WHI P154