Increased rigidity and priming of polymorphonuclear leukocytes in sepsis

E M Drost1, G Kassabian, H J Meiselman

  • 1Departments of Medicine and of Physiology and Biophysics, University of Southern California School of Medicine, Los Angeles, California, USA.

Insights

Polymorphonuclear leukocytes (PMN) show increased rigidity in severe sepsis, potentially causing organ dysfunction. This PMN rigidity improved in survivors, correlating with clinical recovery, suggesting a link to sepsis progression.

Area of Science:

  • Immunology
  • Pathophysiology
  • Biomedical Engineering

Background:

  • Abnormal mechanical properties of polymorphonuclear leukocytes (PMN) may contribute to capillary retention in sepsis.
  • This retention can lead to organ dysfunction during severe sepsis.

Purpose of the Study:

  • To determine if PMN rigidity increases in severe sepsis.
  • To investigate the correlation between PMN rheologic behavior and the clinical course of sepsis.

Main Methods:

  • Micropore filtration using a cell transit analyzer to assess PMN deformation.
  • Studied 18 adults with severe sepsis over 14 days, comparing them to 5 healthy controls.

Main Results:

  • PMN rigidity was 2.5-fold greater in sepsis patients on Day 0 (p < 0.001).
  • PMN rigidity improved in recovering patients but not in those who died, correlating with clinical indicators.
  • Patient PMN showed a 5-fold greater rigidity increase in response to fMLP compared to controls.

Conclusions:

  • Circulating PMN are more rigid and primed for augmented chemotactic response in severe sepsis.
  • Cytokine-mediated increases in PMN rigidity may cause capillary sequestration and impair microvascular perfusion in sepsis.

Related Concept Videos

Acute Inflammation III: Local and Systemic Effects01:25

Acute Inflammation III: Local and Systemic Effects

Acute inflammation produces a coordinated set of local and systemic changes that limit injury, eliminate pathogens, and initiate repair. These responses arise within minutes of infection, trauma, or chemical insult and are driven by vascular alterations and leukocyte-derived mediators. When the stimulus resolves, the reaction typically abates within days.Local EffectsAt the site of injury, arteriolar vasodilation increases blood flow, resulting in redness and warmth. Simultaneously, increased...
Bacterial Meningitis II: Pathophysiology01:26

Bacterial Meningitis II: Pathophysiology

Bacterial meningitis typically begins when pathogens such as Neisseria meningitidis and Streptococcus pneumoniae colonize the nasopharynx and invade the bloodstream. This process is facilitated by bacterial virulence factors, such as polysaccharide capsules, which resist phagocytosis and complement-mediated killing. Less commonly, bacteria reach the central nervous system via contiguous spread from infections like otitis media or sinusitis, through congenital or acquired dural defects, or...
Bacterial Meningitis01:24

Bacterial Meningitis

Bacterial meningitis is a severe infectious disease involving inflammation of the meninges, the protective membranes surrounding the brain and spinal cord. It occurs when pathogenic bacteria cross the blood–brain barrier and enter the cerebrospinal fluid. Common causative organisms include Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, Listeria monocytogenes, and Escherichia coli K1. The exact route of entry varies by pathogen and host condition.Routes of Entry...
Acute Inflammation II: Cellular Phase01:26

Acute Inflammation II: Cellular Phase

The cellular phase of acute inflammation is a tightly orchestrated sequence of events that recruits leukocytes, primarily neutrophils, to sites of tissue injury or infection. Following the initial vascular changes, this phase ensures effective immune cell migration, activation, and function at the affected site to eliminate pathogens and initiate tissue repair.Leukocyte Recruitment CascadeLeukocyte recruitment happens in four steps: margination, adhesion, transmigration, and chemotaxis. Reduced...
Bacterial Meningitis I: Introduction01:22

Bacterial Meningitis I: Introduction

Bacterial meningitis is a severe, life-threatening inflammation of the meninges, particularly the pia mater and arachnoid mater, affecting the subarachnoid space, ventricles, and cerebrospinal fluid (CSF). If untreated, it can lead to significant neurological complications or death.Causative AgentsCommon pathogens vary with age and immune status. In adults, major organisms include Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae. Streptococcus agalactiae (group B...