Blood Cells - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 96

β 2 -integrin ligand [ 186 , 187 ]. 76
Consequently, different proteins preclude inflammation, as they impede either
selectin- or integrin-dependent leukocyte adhesion.

competes for integrin binding with ICAM1, a major

3.7.3.6 Neutrophils in Lungs

Alveolar type-2 cells 77 release granulocyte colony-stimulating factor (CSF3), 78
interleukin-8, and leukotriene-B4 to attract neutrophils [ 188 ]. These chemoattrac-
tants are synthesized not only in alveolar and airway epithelial cells, but also in
endothelial cells and fibroblasts. Interleukin-1 β α

, bacterial
lipopolysaccharide, and bradykinin stimulate the release of these chemoattractants,
particularly CSF3.
In addition, alveolar type-2 epithelial cells secrete interleukin-6, chemokines
CCL2 79 and CCL5, 80 granulocyte-macrophage colony-stimulating factor (CSF2),
transforming growth factor-

, tumor-necrosis factor-

β α β

, constitutively and in response to TNF and IL1

[ 188 ].
In humans, major chemoattractants for neutrophils during lung inflammation
are Glu-Leu-Arg (or ELR) motif-containing (ELR

+

) CXC chemokines that in-
clude CXCL1, CXCL2 and CXCL3, and CXCL8 (IL8). The receptors for these
chemoattractants are CXCR1 and CXCR2 in humans. Matrix constituent-derived
peptides can also behave as chemoattractants. Certain collagen fragments can
provoke accumulation of pulmonary neutrophils. The tripeptide N acetyl Pro-Gly-
Pro (or PGP) that arises from the breakdown of matrix constituents after exposure
to lipopolysaccharides in mouse lungs and can be detected in patients with chronic
obstructive pulmonary disease fosters chemotaxis of neutrophils and production of
superoxide via CXCR1 and CXCR2 receptors [ 189 ]. 81

76 In particular, it blocks

2 -integrin-dependent adhesion and homing of endothelial progenitor
cells to ischemic tissues, hence reducing angiogenesis [ 187 ].
77 Alveolar type-2 cell synthesizes and secretes surfactant. It controls the volume and composition
of the epithelial lining fluid. It proliferates and differentiates into alveolar type-1 cells after lung
injury to maintain the integrity of the alveolar wall. It contributes to the immune response in the
alveolar space.
78 Factor CSF3 is also produced in macrophages, lymphocytes, fibroblasts, and endothelial cells.
79 A.k.a. monocyte chemoattractant protein MCP1.
80 A.k.a. regulated on activation normal T cells expressed and secreted (RANTES).
81 Several matrix proteins contain the PGP motif, especially collagen, but also elastin and
surfactant protein-A and -D. Collagenases, such as MMP1 and MMP9, expose normally hidden
PGP-containing proteic segments, thereby unmasking pro-inflammatory activity of structural
constituent-derived peptides. Neutrophils or macrophages release elastases and several MMP
species in response to inflammatory stimuli.

β