Top

We are now open at our new location. If you had an appt that was missed our team will be reaching out to reschedule. Please call to confirm your appt prior to making the trip.

Schedule Your Appointment Call Us 850-215-3062

  • Home
  • About Us
  • Specialties
    • Osteoarthritis
    • Rheumatoid Arthritis
    • Connective Tissue Diseases
    • Psoriatic Arthritis
    • Gout
    • Fibromyalgia
    • Osteoporosis
    • Polymyalgia Rheumatica
  • Resources
    • Patient Forms
    • Resource Links
  • Recent News
  • Contact Us
  • Home
  • About Us
  • Specialties
    • Osteoarthritis
    • Rheumatoid Arthritis
    • Connective Tissue Diseases
    • Psoriatic Arthritis
    • Gout
    • Fibromyalgia
    • Osteoporosis
    • Polymyalgia Rheumatica
  • Resources
    • Patient Forms
    • Resource Links
  • Recent News
  • Contact Us

Gout Study

February 3, 2014

Transglutaminase 2 limits murine peritoneal acute gout-like inflammation by regulating macrophage clearance of apoptotic neutrophils.

Objective

Monosodium urate monohydrate (MSU) crystals have remarkable inflammatory potential.

Gouty inflammation is spontaneously self-limited, an occurrence recognized since antiquity. Gouty synovitis is driven and sustained by neutrophil influx. Importantly, macrophage phagocytosis of apoptotic (but not necrotic) neutrophils is anti-inflammatory.

Therefore, we tested the hypothesis that efficient clearance of apoptotic neutrophils my macrophages is one of the factors that restrains the progression of gouty inflammation. Macrophage expression of transglutaminase 2 (TG2), a multifunctional protein with reciprocally regulated transamidation and purine nucleotide-binding activities, promotes apoptotic leukocyte uptake.

In this study, we tested the specific role of macrophage TG2 expression in MSU crystal-induced inflammation.

Methods

We studied MSU crystal-induced peritonitis in TG2-/- and congenic TG2+/+ mice. We also studied the effects of TG2 on apoptotic cell uptake by cultured macrophages.

Results

TG2-/- mice demonstrated more progressive neutrophilic accumulation tha did TG2=/+ mice, which was associated with delayed clearance of apoptotic neutrophils during MSU crystal-induced peritonitis. We observed defective phagocytosis of apoptotic leukocytes by TG2-/- peritoneal macrophages, which was corrected by soluble extracellular TG2. Transamidation catalytic activity of TG2 was not required to mediate macrophage uptake of apoptotic leukocytes. In contrast, the TG2 nucleotide binding site residue K173 was critical for this TG2 function. TG2 bound to GDP, ADP, or ATP (but not to GTP) rescued defective apoptotic leukocyte uptake by TG2-/- macrophages.

Conclusion

Enhancement of apoptotic neutrophil uptake by macrophage-derived TG2 restrains gout-like neutrophilic peritoneal inflammation. Differential binding of TG2 by purine nucleotides may contribute to clinical variability in the extent and duration of gouty inflammation.

OUR SPECIALTIES

  • Osteoarthritis
  • Rheumatoid Arthritis
  • Connective Tissue Disease
  • Psoriatic Arthritis
  • Gout
  • Fibromyalgia
  • Osteoporosis
  • Polymyalgia Rheumatica

CONTACT INFO

Bay Arthritis Institute

2401 State Avenue Suite 100

Panama City, FL 32405

M-Th: 8am-Noon & 1pm-5pm

Friday: 8am-1pm

Closed For Lunch

850-215-3062 Phone

850-215-3024 Fax

10800 Panama City Beach Parkway

Panama City Beach, FL 32407

M-Th: 8am-Noon & 1pm-4pm

Friday: 8am-Noon

Closed For Lunch

850-303-6335 Phone

850-588-6866 Fax

Suffering... You deserve a life without pain! From mild to severe pain, early and aggressive treatment is important. When the discomfort is there, Dr. agha can help you using the most current therapy and care.

  • Home
  • About Us
  • Specialties
  • Resources
  • Contact Us
  • Login

Bay Arthritis Institute 2018

Managed by Curiosity Marketing Group

Post navigation

Do You Have Fibromyalgia?