Macrophage phagocytosis of apoptotic neutrophils is compromised by matrix proteins modified by cigarette smoke and lipid peroxidation products

doi:10.1016/j.bbrc.2004.04.003

Biochemical and Biophysical Research Communications

Volume 318, Issue 1, 21 May 2004, Pages 32-37

https://doi.org/10.1016/j.bbrc.2004.04.003 Get rights and content

Abstract

Clearance of apoptotic cells by phagocytosis plays an important role in the resolution of an inflammatory response. Macrophages interacting with extracellular matrix (ECM) proteins upregulate their phagocytic capacity. Cigarette smoke contains highly reactive carbonyls that modify proteins which directly/indirectly affects cellular function. We observed, in vitro, that human macrophages interacting with carbonyl or cigarette smoke modified ECM proteins dramatically down regulated their ability to phagocytose apoptotic neutrophils. We also show that this interaction with carbonyl-adduct modified ECM proteins led to increased macrophage adhesion in vitro. We hypothesise that changes in the ECM environment as a result of cigarette smoking affect the ability of macrophages to remove apoptotic cells. Moreover, we postulate that this decreased phagocytic activity was as a result of sequestration of receptors involved in the uptake of apoptotic cells towards that of recognition of carbonyl adducts on the modified ECM proteins leading to increased macrophage adhesion.

Section snippets

Materials and methods

Preparation and culture of human monocyte derived macrophages from healthy non-smokers. Human peripheral blood cells were separated into mononuclear cells and granulocytes from fresh, citrated blood of healthy volunteers by dextran sedimentation and discontinuous PBS-Percoll density gradient centrifugation as described [13]. Human monocytes were isolated from the mononuclear cells by plating out the mononuclear cell fraction (PBS-Percoll interphase fraction) into 48-well tissue culture plates

Results and discussion

Many factors have been shown to upregulate the nonphlogistic clearance of apoptotic leukocytes by phagocytosis, such as lipoxins, cytokines, and corticosteroids [14], [15], [29]. Interaction of macrophages with ECM components such as fibronectin through the β1 integrin receptors [11] and collagen through Fc receptors can also upregulate phagocytosis. In this study we have investigated the impact of modification of ECM proteins by cigarette smoke and its constituents, namely reactive aldehydes

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Macrophage phagocytosis of apoptotic neutrophils is compromised by matrix proteins modified by cigarette smoke and lipid peroxidation products

Abstract

Section snippets

Materials and methods

Results and discussion

Chest

Trends Pharmacol. Sci.

J. Biol. Chem.

Free Radic. Biol. Med.

Trends Cardiovasc. Med.

Free Radic. Biol. Med.

J. Biol. Chem.

Immunol. Today

J. Biol. Chem.

Granulocyte apoptosis and its role in the resolution and control of lung inflammation

Am. J. Respir. Crit. Care Med.

Inflammatory cells and mediators in bronchial lavage of patients with chronic obstructive pulmonary disease

Eur. Respir. J.

The macrophage in chronic obstructive pulmonary disease

Am. J. Respir. Crit. Care Med.

CD8+ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease

Am. J. Respir. Crit. Care Med.

Cellular and structural bases of chronic obstructive pulmonary disease

Am. J. Respir. Crit. Care Med.

Resolution of lung inflammation by CD44

Science

Phagocytosis of apoptotic neutrophils does not induce release of thromboxane B2

J. Leukocyte Biol.

Regulation of macrophage phagocytosis of apoptotic cells by cAMP

J. Immunol.

Regulation of macrophage phagocytosis of apoptotic neutrophils by adhesion to fibronectin

J. Leukocyte Biol.

CD8⁺ T-lymphocytes in peripheral airways of smokers with chronic obstructive pulmonary disease