Effects of endotoxin on expression of VLA integrins by human bronchoalveolar lavage macrophages

Kang, Yong-Cheol; Lee, Che-Hung; Brummel, Sara; Newball, Harold H.; Forrester, J. V.

doi:10.1002/jlb.57.4.624

Cited by 19 publications

(12 citation statements)

References 42 publications

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“…As with surfactant proteins, this interaction may not directly facilitate phagocytosis by the alveolar macrophages, although it is known that other actions of the macrophages, such as the release of tumor necrosis factor alpha, are enhanced by this interaction (44). Typically, these adhesion molecules bind to subsets of integrins on the surface of macrophages and other cells (6), many of which exhibit dynamic changes in expression during periods of inflammation (24,25). Finally, immunoglobulins against P. carinii can potentially opsinize Pneumocystis organisms and promote phagocytosis or extracellular killing of the pathogens, although the importance of this during in vivo infections is still not clear (reviewed in reference 2).…”

Section: Discussionmentioning

confidence: 99%

Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility toPneumocystis cariniiInfection In Vivo

et al. 2003

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Host defense against the opportunistic pathogen Pneumocystis carinii requires functional interactions of many cell types. Alveolar macrophages are presumed to be a vital host cell in the clearance of P. carinii, and the mechanisms of this interaction have come under scrutiny. The macrophage mannose receptor is believed to play an important role as a receptor involved in the binding and phagocytosis of P. carinii. Although there is in vitro evidence for this interaction, the in vivo role of this receptor in P. carinii clearance in unclear. Using a mouse model in which the mannose receptor has been deleted, we found that the absence of this receptor is not sufficient to allow infection by P. carinii in otherwise immunocompetent mice. Furthermore, when mice were rendered susceptible to P. carinii by CD4؉ depletion, mannose receptor knockout mice (MR-KO) had pathogen loads equal to those of wild-type mice. However, the MR-KO mice exhibited a greater influx of phagocytes into the alveoli during infection. This was accompanied by increased pulmonary pathology in the MR-KO mice, as well as greater accumulation of glycoproteins in the alveoli (glycoproteins, including harmful hydrolytic enzymes, are normally cleared by the mannose receptor). We also found that the surface expression of the mannose receptor is not downregulated during P. carinii infection in wild-type mice. Our findings suggest that while the macrophage mannose receptor may be important in the recognition of P. carinii, in vivo, this mechanism may be redundant, and the absence of this receptor may be compensated for.Pulmonary host defense typically involves cooperation among many cell types, including resident epithelium and macrophages as well as circulating inflammatory cells. However, the importance of each type of cell may differ, depending on the nature of the pathogen presented. Infection with the opportunistic fungus Pneumocystis carinii, which causes often-fatal pneumonia in immunocompromised patients, is an example of a disease process in which many cell types have important but distinct roles. The appearance of antibodies against P. carinii by age 2 in most children, coupled with the low occurrence of the disease in healthy people, led early investigators to conclude that humoral immunity and B cells were of primary importance in host defense against P. carinii (reviewed in reference 68). However, the high incidence of P. carinii infections in AIDS patients (42, 43) and later experimental mouse models highlights the crucial importance of CD4 ϩ lymphocytes in the control of P. carinii infections (5,20).In spite of their importance, CD4 ϩ lymphocytes are probably not involved with the major effector mechanisms against P. carinii (21, 52); instead, this role probably falls to CD8 ϩ lymphocytes, antibodies, and macrophages. Although the importance of CD8 ϩ cells in defense against P. carinii (3, 27) as well as their role in host tissue damage (74) is evident, the mechanisms by which these cells cause these responses are not clear. And although ther...

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Section: Discussionmentioning

confidence: 99%

Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility toPneumocystis cariniiInfection In Vivo

et al. 2003

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“…In context of this observation, it is interesting that adhesion molecule expression on in vitro-generated human M2 macrophages (M-CSF derived) is more sensitive to CCL1 than that on M1 macrophages (GM-CSF derived). Kang et al have previously demonstrated that prolonged exposure to LPS downregulates expression of certain VLA components, while brief transient exposure upregulates expression (18). Our observations suggest that M2 macrophages may be more involved in conditions such as peritoneal adhesion surgery complications and that CCL1 may play a contributing role.…”

Section: Discussionmentioning

confidence: 49%

CCR8 Signaling Influences Toll-Like Receptor 4 Responses in Human Macrophages in Inflammatory Diseases

Reimer

Brange

Rosendahl

2011

Clin Vaccine Immunol

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CCR8 immunity is generally associated with Th2 responses in allergic diseases. In this study, we demonstrate for the first time a pronounced attenuated influx of macrophages in ovalbumin (OVA)-challenged CCR8 knockout mice. To explore whether macrophages in human inflamed lung tissue also were CCR8 positive, human lung tissue from patients with chronic obstructive pulmonary disease (COPD) was evaluated. Indeed, CCR8 expression was pronounced in invading monocytes/macrophages from lungs of patients with Global Initiative for Obstructive Lung Disease (GOLD) stage IV COPD. Given this expression pattern, the functional role of CCR8 on human macrophages was evaluated in vitro. Human peripheral blood monocytes expressed low levels of CCR8, while macrophage colony-stimulating factor (M-CSF)-derived human macrophages expressed significantly elevated surface levels of CCR8. Importantly, CCL1 directly regulated the expression of CD18 and CD49b and hence influenced the adhesion capacity of human macrophages. CCL1 drives chemotaxis in M-CSF-derived macrophages, and this could be completely inhibited by lipopolysaccharide (LPS). Whereas both CCL1 and LPS monotreatment inhibited spontaneous superoxide release in macrophages, CCL1 significantly induced superoxide release in the presence of LPS in a dose-dependent manner. Finally, CCL1 induced production of proinflammatory cytokines such as tumor necrosis factor alpha (TNF-␣) and interleukin-6 (IL-6) and could inhibit LPS-induced cytokine production in a dose-dependent manner. Our data demonstrate, for the first time, the presence of CCR8 on inflammatory macrophages in human COPD lung tissue. Importantly, the functional data from human macrophages suggest a potential cross talk between the CCR8 and the Toll-like receptor 4 (TLR4) pathways, both of which are present in COPD patients.

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“…decrease in macrophage phagocytosis of yeast (Sandstrom et al, 1992), and treatment of AM with LPS decreased the expression of various b 1 integrins including fibronectin receptors (Kang et al, 1995). Data showed that the chemiluminescence response to opsonized zymosan was not affected by endotoxin in either MO or AM, but was decreased by UAP.…”

Section: Discussionmentioning

confidence: 96%

Decreased Cd11b Expression, Phagocytosis, and Oxidative Burst in Urban Particulate Pollution-Exposed Human Monocytes and Alveolar Macrophages

Becker¹

1998

Journal of Toxicology and Environmental Health, Part A

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Elevated levels of air pollution particulates < or = 10 microm in diameter (PM10) have been associated with an increase in mortality and morbidity due to pulmonary complications, including pneumonia. Impairment of inflammatory and host defense functions of the alveolar macrophage (AM) may be a precipitating factor. The present study was undertaken to determine whether human AM and blood derived monocytes (MO) modulate the expression of receptors important for phagocytosis of opsonized microbes (CD11b, CD11c), gram-negative bacteria (CD14), extracellular matrix interaction (CD29), and immune responses (CD11a, CD54, HLA-DR) when exposed to particulates obtained from urban air (UAP). Furthermore, phagocytosis of and oxidant generation by opsonized yeast were investigated in particle-exposed cells. AM and MO exposed to UAP for 18 h expressed significantly lower levels of CD11b and CD29. CD14 expression was markedly decreased in MO but not in AM, and CD11c was reduced in AM but not in MO. CD11a, CD54, and HLA-DR were unaltered in both phagocyte populations. Decreased receptor expression was not dependent on particle load in the cells. Phagocytosis of Saccharomyces cerevisiae and the chemiluminescence response were also significantly inhibited by UAP. Time-course studies revealed that decreased oxidant generation was evident already at 3 h postexposure, while significant effects on phagocytosis and CD11b expression were found at 18 h. These data indicate that exposure to particulate pollution is likely to impair host defense functions of AM and MO, which are important in elimination of a variety of pathogens in the lung.

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Effects of endotoxin on expression of VLA integrins by human bronchoalveolar lavage macrophages

Cited by 19 publications

References 42 publications

Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility toPneumocystis cariniiInfection In Vivo

Absence of the Macrophage Mannose Receptor in Mice Does Not Increase Susceptibility toPneumocystis cariniiInfection In Vivo

CCR8 Signaling Influences Toll-Like Receptor 4 Responses in Human Macrophages in Inflammatory Diseases

Decreased Cd11b Expression, Phagocytosis, and Oxidative Burst in Urban Particulate Pollution-Exposed Human Monocytes and Alveolar Macrophages

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