Mice Lacking beta2-Integrin Function Remain Glucose Tolerant in Spite of Insulin Resistance, Neutrophil Infiltration and Inflammation

Morrison, Vicky L.; Sneddon, Claire; Savinko, Terhi; Uotila, Liisa M.; Jalicy, Susan M.; Gabriel, Jennie L.; Li, Kang; Ashford, M. L. J.; Fagerholm, Susanna C.

doi:10.1371/journal.pone.0138872

Cited by 15 publications

(12 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They had about 10-fold increased serum IgG levels, and elevated IL-3 and IL-6 serum levels as compared with WT mice. The CD18 −/− mouse model resembles therefore a severe form of the LAD-I syndrome in humans and has been explored in the context of various pathologies like psoriasis [180], wound healing [181], diabetes [182], carditis [183,184], osteoporosis [185], and infections [186].…”

Section: Mouse Models To Study Functions Of Distinct β2 Integrinsmentioning

confidence: 99%

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

Bednarczyk

Stege

Grabbe

et al. 2020

IJMS

View full text Add to dashboard Cite

β2 integrins are heterodimeric surface receptors composed of a variable α (CD11a-CD11d) and a constant β (CD18) subunit and are specifically expressed by leukocytes. The α subunit defines the individual functional properties of the corresponding β2 integrin, but all β2 integrins show functional overlap. They mediate adhesion to other cells and to components of the extracellular matrix (ECM), orchestrate uptake of extracellular material like complement-opsonized pathogens, control cytoskeletal organization, and modulate cell signaling. This review aims to delineate the tremendous role of β2 integrins for immune functions as exemplified by the phenotype of LAD-I (leukocyte adhesion deficiency 1) patients that suffer from strong recurrent infections. These immune defects have been largely attributed to impaired migratory and phagocytic properties of polymorphonuclear granulocytes. The molecular base for this inherited disease is a functional impairment of β2 integrins due to mutations within the CD18 gene. LAD-I patients are also predisposed for autoimmune diseases. In agreement, polymorphisms within the CD11b gene have been associated with autoimmunity. Consequently, β2 integrins have received growing interest as targets in the treatment of autoimmune diseases. Moreover, β2 integrin activity on leukocytes has been implicated in tumor development.

show abstract

Section: Mouse Models To Study Functions Of Distinct β2 Integrinsmentioning

confidence: 99%

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

Bednarczyk

Stege

Grabbe

et al. 2020

IJMS

View full text Add to dashboard Cite

show abstract

“…These cells transiently infiltrate murine adipose tissue with the initiation of high-fat-diet feeding and mediate insulin resistance in mice. 24 , 25 Natural killer (NK) cells, best known for their role in the early host response to viral infections and in killing tumor cells, have recently been shown to promote macrophage proliferation and polarization in adipose tissue and insulin resistance in mice fed a high-fat diet. 26 …”

Section: Cellular Composition Of Adipose Tissuementioning

confidence: 99%

The role of adipokines in chronic inflammation

Mancuso

2016

ITT

299

252

View full text Add to dashboard Cite

Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function.

show abstract

“…On the other hand, leucocyte-derived β2 integrin has been associated with HFD-induced obesity and insulin resistance in the adipose tissue. Under a HFD condition, mutated β2-integrin knockin mice display increased neutrophil numbers in white adipose tissues and show significantly increased peripheral insulin resistance [72]. The β2 integrin subfamily is comprised of 4 members, αLβ2 (CD11a/CD18), αMβ2 (CD11b/CD18), αXβ2 (CD11c/CD18), and αDβ2 (CD11d/CD18).…”

Section: Ecm Receptors In the Adipose Tissuementioning

confidence: 99%

Adipose extracellular matrix remodelling in obesity and insulin resistance

Lin

Chun

2016

Biochemical Pharmacology

Self Cite

179

130

View full text Add to dashboard Cite

The extracellular matrix (ECM) of adipose tissues undergoes constant remodelling to allow adipocytes and their precursor cells to change cell shape and function in adaptation to nutritional cues. Abnormal accumulation of ECM components and their modifiers in adipose tissues has been recently demonstrated to cause obesity-associated insulin resistance, a hallmark of type 2 diabetes. Integrins and other ECM receptors (e.g. CD44) that are expressed in adipose tissues have been shown to regulate insulin sensitivity. It is well understood that a hypoxic response is observed in adipose tissue expansion during obesity progression and that hypoxic response accelerates fibrosis and inflammation in white adipose tissues. The expansion of adipose tissues should require angiogenesis; however, the excess deposition of ECM limits the angiogenic response of white adipose tissues in obesity. While recent studies have focused on the metabolic consequences and the mechanisms of adipose tissue expansion and remodelling, little attention has been paid to the role played by the interaction between peri-adipocyte ECM and their cognate cell surface receptors. This review will address what is currently known about the roles played by adipose ECM, their modifiers, and ECM receptors in obesity and insulin resistance. Understanding how excess ECM deposition in the adipose tissue deteriorates insulin sensitivity would provide us hints to develop a new therapeutic strategy for the treatment of insulin resistance and type 2 diabetes.

show abstract

Mice Lacking beta2-Integrin Function Remain Glucose Tolerant in Spite of Insulin Resistance, Neutrophil Infiltration and Inflammation

Cited by 15 publications

References 28 publications

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

β2 Integrins—Multi-Functional Leukocyte Receptors in Health and Disease

The role of adipokines in chronic inflammation

Adipose extracellular matrix remodelling in obesity and insulin resistance

Contact Info

Product

Resources

About