It is toxic to parasites, tumor cells, and host tissue; causes histamine release; inhibits heparin activity.
It inactivates leukotrienes.
20 to 40 μm or larger
The release of calcium stored in the endoplasmic reticulum triggers the respiratory (oxidative) burst in neutrophils.
Segmented nucleus
Myeloperoxidase, Lysozyme–bactericidal factors, Cationic proteins, Acid hydrolases, Elastase, Nonspecific collagenase, BPI, Defensins, Cathepsin G, Phospholipase A2
12 to 15 μm
17 to 30 μm or larger
In LAD type I, the defect is a lack of functional expression of the β2 integrins.
Neutrophils kill microbes through lysosomal degradation, phagocytosis, and the formation of phagolysosomes.
ICAM-1 interacts with CD11/CD18 integrins (LFA-1, Mac-1) to mediate adhesion, arrest, and transmigration of all leukocytes.
Eosinophils release mediators in response to helminthic infections, contributing to the immune response against these parasites.
Neutrophils are confined to the vascular lumen and do not pass across the vascular wall, despite the bacterial stimulus.
Leukocytes
β2 integrins
7.0 μm
Lactoferrin inhibits the growth of phagocytosed bacteria by sequestering free iron.
NETs (neutrophil extracellular traps) are composed of a DNA backbone embedded with antimicrobial peptides and proteins, and they entrap bacteria and can be microbicidal.
Receptors on neutrophils that bind inflammatory mediators include receptors for PAF, C5a, IL-8, substance P (the neurokinin-1 receptor), LTs, kallikrein, GM-CSF, and cytokines such as TNF.
12-15 μm
12-20 μm
VLA-1 (CD49a/CD29) and VLA-2 (CD49b/CD29)
20 to 30 μm or larger
NADPH oxidase catalyzes the formation of superoxide free radicals used to kill microbes or degrade internalized material.
Efalizumab, an antibody to αLβ2 integrin (LFA-1).
SNPs are variations in a single nucleotide that can affect the expression level and activity of inflammatory genes, altering the type and magnitude of inflammatory responses.
Oxygen-independent antimicrobial mechanisms include cathepsin G and elastase (damage to microbial membranes), low-molecular-weight defensins, high-molecular-weight cationic proteins, bactericidal permeability-increasing protein, lactoferrin (complex with iron), lysozyme (splits proteoglycan), and acid hydrolases (degrade dead microbes).
Lactoferrin, Lysozyme, Alkaline phosphates, Type IV collagenase, Leukocyte adhesion molecules, Plasminogen activation, Phospholipase A2
ICAM-1
E-selectin (CD62E)
The three types of leukocyte adhesion deficiencies are LAD type I, LAD type II, and LAD type III.
P-selectin, interacting with Sialyl Lewis X and PSGL-1, mediates the rolling of neutrophils, monocytes, and lymphocytes.
Laminitis, reperfusion injury of intestine after colic, gastric dilation/volvulus, mastitis, enteritis, allergic lung disease, pneumonia, and autoimmune diseases.
Hypoxic conditions stabilize hypoxia-inducible factor-1α (HIF-1α) in neutrophils during intense inflammation.
In Irish setters with CLAD, there is a single missense mutation resulting in a G to C transversion at nucleotide 107 of the cDNA sequence, resulting in a serine that replaces a highly conserved cysteine.
The primary defect is the lack of CD18 expression, which impairs neutrophil stable adherence and migration across the vascular wall.
VCAM-1
12 to 18 μm
The migration of neutrophils is initiated by chemotactic gradients and inflammatory mediators.
Cattle with BLAD develop severe oral ulcers, gingivitis, tooth loss, enteric ulcers, cutaneous ulcers, abscesses that lack pus formation, and pneumonia.
Stroke, myocardial infarction, asthma, and autoimmune diseases.
Eosinophil products, such as basic proteins and oxidative radicals, contribute to tissue damage in organs like the lungs (asthma), heart, skin, and gastrointestinal tract.
Eosinophil cationic protein exerts biological effects on microbes and the tissue in which they replicate by damaging lipid membranes.
NADPH oxidase generates superoxide anion during the oxidative burst, which leads to the formation of further microbial agents such as hydrogen peroxide and hypochlorite anion.
9-12 μm
Binds to PECAM-1 on endothelial cells and leukocytes
The main types of adhesion molecules are selectins, integrins, cytoadhesins, the immunoglobulin superfamily, and other molecules such as CD44.
Inhibition of integrin-associated proteins such as paxillin, talin effects on β2 integrins, and inhibition of membrane protein CD98 to regulate β1 and β3 integrins.
The principal opsonin receptors present on neutrophil membranes are complement (CR1 and CR3) and Fc receptors (Fcγ-receptor I, IIA, IIIB).
Lymphocytes, macrophages, and plasma cells are present in the perivascular areas of Peyer’s patches, but the surrounding lymphoid tissue virtually lacks neutrophils.
5.7 μm
12 to 20 μm
6.0 μm
Neutrophils generate hypochlorous acid through the enzyme myeloperoxidase, which converts hydrogen peroxide to hypochlorous acid.
The four distinct basic proteins are major basic protein (MBP), eosinophil cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase.
αIIbβ3 (CD41/CD61)
LAD type II is caused by a mutation in a fucose transporter gene, leading to a lack of fucosylated sialyl Lewis X used for selectin-mediated adherence.
LAD type IV involves decreased expression of β2 and α4β1 integrins due to a mutation in the cystic fibrosis transmembrane conductance regulator receptor (CFTR receptor).
Natalizumab, an antibody to α4β1 integrin, reduces the severity of multiple sclerosis and Crohn’s disease.
Neutrophils entering activated venules screen the area for activated platelets and inflammatory mediators, then distribute receptors in a polarized manner to drive directed migration to the inflammatory site for phagocytosis, microbial killing, and release of inflammatory mediators.
Some isoforms, when bound to receptors like VEGFR-2, reduce rather than enhance signaling.
The oral cavity has irregularly arranged molar teeth, oral ulcers, and grass material within the oral cavity secondary to impaired mastication.
15 to 25 μm
LAD type III is caused by a defect in kindlin-3, a cytoplasmic protein essential for integrin activity in the cytosol.
During the resolution of acute inflammation, growth factor withdrawal induces apoptosis in neutrophils, which can be accelerated by TNF.
Low gene copy numbers result in limited production of antimicrobial peptides even in the presence of inflammatory stimuli.
7.0 μm
It is toxic to parasites, causes histamine release, and has antiparasitic properties.
9 to 12 μm
Cytokines such as IL-1 and TNF, and growth factors such as GM-CSF, G-CSF, and IL-3 maintain neutrophil concentrations.
Common symptoms include severe oral ulcers, gingivitis, tooth loss, enteric ulcers, cutaneous ulcers, abscesses that lack pus formation, and pneumonia.
HIF-1α induces transcription of genes that promote phagocytosis, inhibition of apoptosis, release of antimicrobial peptides, granule proteases, VEGF, cytokine release, and inducible NO synthase (iNOS).
They result in the truncation of mRNA and protein products, leading to altered or non-functional inflammatory molecules.
12-18 μm
β1 integrins
It has microbicidal properties.
VCAM-1 (CD106)
12 to 20 μm
The mutation is a single-point mutation (adenine → guanine) at position 128 resulting in a single amino acid change (aspartic acid → glycine) in the β-subunit (CD18) of the β2 integrins.
The guanosine triphosphatase (GTPase) Rac1 initiates activity in neutrophils, leading to actin assembly for the formation of filopodia or lamellipodia, which surround and internalize particles via phagocytosis.
Round to oval eccentric 'cartwheel-shaped' nucleus
The serosa of the small intestine is thickened, with fibrous tags between serosal surfaces. The mucosa underlying the thickened serosa is ulcerated and covered by cell debris, and vascular lumina contain elevated numbers of neutrophils that do not adhere to the vascular endothelium.
It is neurotoxic with H2O2/halide and has microbicidal properties.
15 to 30 μm
Neutrophils primarily function to kill microbes, kill tumor cells, and eliminate foreign materials through phagocytosis and secretion of granule contents.
Defensins and cathelicidins contribute to the degradation of microbes by forming pores in microbial membranes and affecting chemotaxis and activation of the adaptive immune response.
Primary granules, also known as azurophilic granules, contain myeloperoxidase, elastase, defensins, and small amounts of lysozyme.
Intravascular neutrophils partially adhered (rolling) on endothelial cells in the capillary of the alveolar septum in the lung.
Latent forms are present within the tissue stroma and become functional upon activation by MMPs.
12-18 μm
Nociceptors are activated by transient receptor potential (TRP) receptors and G protein–coupled receptors (GPCRs) that respond to chemicals, heat/cold, mechanical injury, ATP, and inflammatory mediators such as bradykinin, histamine, and cytokines.
The hallmark lesion is a sparse infiltration of neutrophils into ulcerated mucosal surfaces or pulmonary alveoli, despite high numbers of neutrophils within the lumen of submucosal and pulmonary septal blood vessels.
They bind ligands but do not transmit signals because the receptor is detached from a cell.
Activated macrophages can be up to twice as large as resting macrophages and have more vacuoles due to the synthesis of cytoplasmic lysosomal enzymes.
20-40 μm or larger
