Induction of a potential paracrine angiogenic loop between human THP-1 macrophages and human microvascular endothelial cells during Bartonella henselae infection.
Bartonella henselae is responsible for various disease syndromes that loosely correlate with the immune status of the host. In the immunocompromised individual, B. henselae-induced angiogenesis, or bacillary angiomatosis, is characterized by vascular proliferative lesions similar to those in Kaposi's sarcoma. We hypothesize that B. henselae-mediated interaction with immune cells, namely, macrophages, induces potential angiogenic growth factors and cytokines which contribute in a paracrine manner to the proliferation of endothelial cells. Vascular endothelial growth factor (VEGF), a direct inducer of angiogenesis, and interleukin-1beta (IL-1beta), a potentiator of VEGF, were detected within 12 and 6 h, respectively, in supernatants from phorbol 12-myristate 13-acetate-differentiated human THP-1 macrophages exposed to live B. henselae. Pretreatment of macrophages with cytochalasin D, a phagocytosis inhibitor, yielded comparable results, suggesting that bacterium-cell attachment is sufficient for VEGF and IL-1beta induction. IL-8, an angiogenic cytokine with chemotactic properties, was induced in human microvascular endothelial cells (HMEC-1) within 6 h of infection, whereas no IL-8 induction was observed in infected THP-1 cells. In addition, conditioned medium from infected macrophages induced the proliferation of HMEC-1, thus demonstrating angiogenic potential. These data suggest that Bartonella modulation of host or target cell cytokines and growth factors, rather than a direct role of the bacterium as an endothelial cell mitogen, is the predominant mechanism responsible for angiogenesis. B. henselae induction of VEGF, IL-1beta, and IL-8 outlines a broader potential paracrine angiogenic loop whereby macrophages play the predominant role as the effector cell and endothelial cells are the final target cell, resulting in their proliferation.
Resto-Ruiz
Sandra I
SI
University of South Florida, College of Medicine, Department of Medical Microbiology and Immunology, Tampa 33612, USA.
Schmiederer
Michael
M
Sweger
Debra
D
Newton
Catherine
C
Klein
Thomas W
TW
Friedman
Herman
H
Anderson
Burt E
BE
D018416:Bartonella henselae / Q000276:immunology*; D002196:Capillaries / Q000166:cytology; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D015638:Cytochalasin D / Q000494:pharmacology; D016228:Endothelial Growth Factors / Q000096:biosynthesis* / Q000276:immunology; D004730:Endothelium, Vascular / Q000166:cytology; D006801:Humans; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000276:immunology; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000276:immunology; D008222:Lymphokines / Q000096:biosynthesis* / Q000276:immunology; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D009000:Monocytes / Q000187:drug effects / Q000276:immunology / Q000382:microbiology; D009389:Neovascularization, Pathologic / Q000276:immunology*; D019384:Nucleic Acid Synthesis Inhibitors / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016228:Endothelial Growth Factors; D007375:Interleukin-1; D016209:Interleukin-8; D008222:Lymphokines; D019384:Nucleic Acid Synthesis Inhibitors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015638:Cytochalasin D