Sterile inflammation alters neutrophil kinetics in mice

Alakesh, Alakesh; Jothiprakasam, Thiruvickraman; Raghavan, Jayashree Vijaya; Jhunjhunwala, Siddharth

doi:10.1002/jlb.1a0321-132rr

Cited by 6 publications

(3 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…We observed an increased percentage and numbers of both monocytes and neutrophils in circulation in the diabetic mice compared to WT mice (Figure ), similar to an observation made in individuals with type 2 diabetes by Zhang and colleagues . We also observed an increased number of immature neutrophils in the circulation of diabetic mice (Figure ), which usually occurs during active and sustained inflammation that causes a reduction in the maturation time of these cells in the bone marrow. , Additionally, these mice show deficits in the upregulation of CXCR4 post-activation (Figure ). CXCR4 is required for reverse migration of neutrophils to the bone marrow from circulation .…”

Section: Discussionsupporting

confidence: 87%

“…40 We also observed an increased number of immature neutrophils in the circulation of diabetic mice (Figure 2), which usually occurs during active and sustained inflammation that causes a reduction in the maturation time of these cells in the bone marrow. 41,42 Additionally, these mice show deficits in the upregulation of CXCR4 post-activation (Figure 2). CXCR4 is required for reverse migration of neutrophils to the bone marrow from circulation.…”

Section: ■ Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Immunomodulatory Bandage for Accelerated Healing of Diabetic Wounds

Raghavan

Dorai

Sagar

et al. 2022

ACS Bio Med Chem Au

Self Cite

View full text Add to dashboard Cite

Diabetic foot ulcers are challenging to treat. Current strategies to treat these wounds focus on preventing infection and promoting tissue regrowth but are ineffective in many individuals. Low-grade chronic inflammation is present in individuals with diabetes, and altering the inflammatory responses at the wound site could be an alternate approach to promote healing. We hypothesized that immunomodulation of the wound microenvironment would result in accelerated healing. To test this hypothesis, we began by characterizing the changes in the myeloid cell phenotype in a mouse model [leptin receptor knockout (KO) mouse] that closely mimics the type 2 diabetes condition observed in humans. We observed increased numbers of monocytes and neutrophils in the circulation of the KO mice compared to that in wild-type control mice. We also observed several phenotypic changes in neutrophils from the KO diabetic mice, suggesting low-grade systemic inflammation. Hence, we developed a rapamycin-loaded chitosan scaffold that may be used to modulate immune responses. The use of these immunomodulatory scaffolds at a wound site resulted in accelerated healing compared to the healing using blank scaffolds. In summary, our data suggest that immunomodulation may be a viable strategy to promote the healing of wounds in individuals with diabetes.

show abstract

Section: Discussionsupporting

confidence: 87%

Section: ■ Discussionmentioning

confidence: 99%

Immunomodulatory Bandage for Accelerated Healing of Diabetic Wounds

Raghavan

Dorai

Sagar

et al. 2022

ACS Bio Med Chem Au

Self Cite

View full text Add to dashboard Cite

show abstract

“…The relevance of our question is supported by the fact that sterile inflammation is induced in many in vivo mouse studies ( 48 , 55 ), yet the role of factors released from damaged or dying cells, such as DAMPs and RAMPs, in triggering inflammation during sterile inflammation is not widely investigated. The different phases involved in tissue damage and regeneration, which heavily rely on the innate immune system, particularly monocyte-derived macrophages.…”

Section: Effect Of Damps and Ramps Released From Dying Cells On Macro...mentioning

confidence: 99%

Damage-mediated macrophage polarization in sterile inflammation

et al. 2023

View full text Add to dashboard Cite

Most of the leading causes of death, such as cardiovascular diseases, cancer, dementia, neurodegenerative diseases, and many more, are associated with sterile inflammation, either as a cause or a consequence of these conditions. The ability to control the progression of inflammation toward tissue resolution before it becomes chronic holds significant clinical potential. During sterile inflammation, the initiation of inflammation occurs through damage-associated molecular patterns (DAMPs) in the absence of pathogen-associated molecules. Macrophages, which are primarily localized in the tissue, play a pivotal role in sensing DAMPs. Furthermore, macrophages can also detect and respond to resolution-associated molecular patterns (RAMPs) and specific pro-resolving mediators (SPMs) during sterile inflammation. Macrophages, being highly adaptable cells, are particularly influenced by changes in the microenvironment. In response to the tissue environment, monocytes, pro-inflammatory macrophages, and pro-resolution macrophages can modulate their differentiation state. Ultimately, DAMP and RAMP-primed macrophages, depending on the predominant subpopulation, regulate the balance between inflammatory and resolving processes. While sterile injury and pathogen-induced reactions may have distinct effects on macrophages, most studies have focused on macrophage responses induced by pathogens. In this review, which emphasizes available human data, we illustrate how macrophages sense these mediators by examining the expression of receptors for DAMPs, RAMPs, and SPMs. We also delve into the signaling pathways induced by DAMPs, RAMPs, and SPMs, which primarily contribute to the regulation of macrophage differentiation from a pro-inflammatory to a pro-resolution phenotype. Understanding the regulatory mechanisms behind the transition between macrophage subtypes can offer insights into manipulating the transition from inflammation to resolution in sterile inflammatory diseases.

show abstract

Eosinophils Respond to Extracellular Matrix Treated Muscle Injuries but are Not Required for Macrophage Polarization

Lokwani,

Fertil,

Hartigan

et al. 2024

Adv Healthcare Materials

View full text Add to dashboard Cite

The immune response to decellularized extracellular matrix (ECM) muscle injury is characterized by Th2 T cells, Tregs, M2‐like macrophages, and an abundance of eosinophils. Eosinophils have previously been described as mediators of muscle regeneration but inhibit skin wound healing. In addition to response to wounding, a large number of eosinophils respond to biomaterial‐treated muscle injury, specifically in response to decellularized ECM. ECM treatment of muscle wounds has been associated with positive outcomes in tissue regeneration, but the detailed mechanisms of action are still being evaluated. Here, this work investigates the role of these eosinophils in terms of their immunologic phenotype and subsequent effect on the local tissue microenvironment. These cells have a mixed phenotype showing both type‐2 and regulatory gene upregulation and but are not required for macrophage polarization. Beyond the local tissue, ECM treatment is seen to induce a transient flux of eosinophils to the lungs but prevented a trauma‐associated neutrophilia in the lungs of injured mice. This work believes this local and systemic immunomodulation contributes to the regenerative effects of the material and such distal tissue effects should be considered in therapeutic design and implementation.

show abstract

Sterile inflammation alters neutrophil kinetics in mice

Cited by 6 publications

References 48 publications

Immunomodulatory Bandage for Accelerated Healing of Diabetic Wounds

Immunomodulatory Bandage for Accelerated Healing of Diabetic Wounds

Damage-mediated macrophage polarization in sterile inflammation

Eosinophils Respond to Extracellular Matrix Treated Muscle Injuries but are Not Required for Macrophage Polarization

Contact Info

Product

Resources

About